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Updated: May 9, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
HSV-NIS, an oncolytic herpes simplex virus type 1 encoding human sodium iodide symporter for preclinical prostate
H Li1, H Nakashima, T D Decklever
1Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Abstract:
Several clinical trials have shown that oncolytic herpes simplex virus type 1 (oHSV-1) can be safely administered to patients. However, virus replication in tumor tissue has generally not been monitored in these oHSV clinical trials, and the data suggest that its oncolytic potency needs to be improved. To facilitate noninvasive monitoring of the in vivo spread of an oHSV and to increase its antitumor efficacy, the gene coding for human sodium iodide symporter (NIS) was incorporated into a recombinant oHSV genome and the corresponding virus (oHSV-NIS) rescued in our laboratory. Our data demonstrate that a human prostate cancer cell line, LNCap, efficiently concentrates radioactive iodine after the cells have been infected in vitro or in vivo. In vivo replication of oHSV-NIS in tumors was noninvasively monitored by computed tomography/single-photon emission computed tomography imaging of the biodistribution of pertechnetate and was confirmed. LNCap xenografts in nude mice were eradicated by intratumoral administration of oHSV-NIS. Systemic administration of oHSV-NIS prolonged the survival of tumor-bearing mice, and the therapeutic effect was further enhanced by administration of (131)I after the intratumoral spread of the virus had peaked. oHSV-NIS has the potential to substantially enhance the outcomes of standard therapy for patients with prostate cancer.
Insights
Oncolytic herpes simplex virus type 1 (oHSV-1) engineered with human sodium iodide symporter (NIS) allows noninvasive monitoring and enhanced tumor eradication. This oHSV-NIS shows promise for improving prostate cancer therapy outcomes.
Area of Science:
- Oncology
- Virology
- Molecular Imaging
Background:
- Oncolytic herpes simplex virus type 1 (oHSV-1) shows safety in clinical trials but lacks effective tumor monitoring and needs improved potency.
- Current oHSV therapies require better methods for tracking in vivo virus spread and enhancing antitumor efficacy.
Purpose of the Study:
- To develop a novel oHSV (oHSV-NIS) incorporating the human sodium iodide symporter (NIS) gene for noninvasive imaging and enhanced efficacy.
- To evaluate the biodistribution, replication, and therapeutic potential of oHSV-NIS in prostate cancer models.
Main Methods:
- Recombinant oHSV-NIS was engineered and rescued.
- Prostate cancer cells (LNCap) were infected in vitro and in vivo.
- Radioiodine uptake was assessed.
- Tumor replication of oHSV-NIS was monitored noninvasively using SPECT/CT imaging.
- Therapeutic efficacy was evaluated in mouse xenograft models.
Main Results:
- Infected LNCap cells efficiently concentrated radioactive iodine.
- oHSV-NIS replication in tumors was successfully monitored noninvasively.
- Intratumoral administration of oHSV-NIS eradicated LNCap xenografts.
- Systemic oHSV-NIS prolonged survival, with enhanced effects when combined with (131)I therapy.
Conclusions:
- oHSV-NIS enables noninvasive monitoring of virus replication in tumors.
- This engineered oncolytic virus demonstrates significant antitumor efficacy in preclinical models.
- oHSV-NIS holds potential for improving prostate cancer treatment outcomes, possibly in conjunction with radioiodine therapy.
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